Pathway Activation Strength (PAS) analysis of microarray data reveal similarities of aging with age-related macular degeneration and Hutchinson-Gilford progeria ? should aging be considered as a disease?

Abstract

Aging is a complex process leading to loss of body and cognitive functions as well as to several age-related diseases. The complexity of human aging has eluded biologists and physicians for decades, leading to a concerted effort to unravel the physiological, cellular and molecular mechanisms of aging. A potentially successful approach involves the analysis of naturally occurring aging disorders [1,2]. For instance, age-related macular degeneration (AMD) is a major cause of blindness in older people with age as the main risk factor (1). Premature aging is particularly manifested in the rare genetic condition, Hutchinson-Gilford Progeria Syndrome (HGPS) (2), which is a disease with major phenotypic features of accelerated aging. However, the contribution of aging to these age-related diseases is still poorly understood. In this research study we compared different tissue-specific pathway activation profiles in normal aging with progeria and AMD. We used GeroScope, a bioinformatics platform that enables calculation of the Pathway Activation Strength (PAS) (3), for qualitative measurement of pathway activation in a relevant set of microarray gene expression data representing aged, AMD and HGPS tissue samples. Here we present data supporting the notion that these age-related diseases share similarity with healthy aging at the signaling pathway level. Therefore, targeting aging-related signaling pathways may be a valuable avenue to identify cures for a variety of age-related diseases, including AMD, HGPS, Alzheimer’s disease and others.